反应详情

温度

100 °C

6-Chloro-nicotinic acid methyl ester (60 g, 0.35 mol) is taken up in 500 mL 2M ethylamine in THF and stirred at 100° C. in a sealed tube for 16 h. The reaction mixture is cooled to RT and the solvents are removed under reduced pressure. The residue is poured on ice and stirred for 15 min. The precipitate is filtered off, washed with water and dried in vacuo. The dried 6-ethylamino-nicotinic acid methyl ester (30 g, 0.17 mol) is dissolved in 150 mL DCM and triethylamine (29 mL, 0.20 mol), DMAP (4.0 g, 33 mmol) and di-tert-butyl to dicarbonate (91.7 g, 0.42 mol) are added successively at 0° C. The reaction mixture is allowed to warm up to RT and stirred for 16 h. To the reaction mixture 100 mL of 10% citric acid in water is added and the reaction mixture is stirred for 10 min. The organic phase is separated, dried over Na2SO4 and concentrated under reduced pressure. Yield: 60 g. The crude 6-(tert-butoxycarbonyl-ethyl-amino)-nicotinic acid methyl ester is taken up in 100 mL dioxane and a solution of lithium hydroxide monohydrate (13.5 g, 0.32 mol) in 100 mL is added and the reaction mixture is stirred at RT for 4 h. The dioxane is removed from the reaction mixture under reduced pressure, water is added and the reaction mixture is acidified to pH 6 with a solution of 10% citric acid in water. The formed precipitate is filtered off and dried in vacuo. Yield: 36 g. 1H NMR (DMSO-d6): δ 13.2 (s, 1H), 8.8 (s, 1H), 8.2 (d, 1H), 7.8 (d, 1H), 4.0 (quart, 2H), 1.5 (s, 9H), 1.2 (t, 3H).

1. temperatureThe reaction mixture is cooled to RT
2. customthe solvents are removed under reduced pressure
3. additionThe residue is poured on ice
4. stirringstirred for 15 min
5. filtrationThe precipitate is filtered off
6. washwashed with water
7. customdried in vacuo
8. temperatureto warm up to RT
9. stirringstirred for 16 h
10. stirringthe reaction mixture is stirred for 10 min
11. customThe organic phase is separated
12. dry with materialdried over Na2SO4
13. concentrationconcentrated under reduced pressure
14. stirringthe reaction mixture is stirred at RT for 4 h
15. customThe dioxane is removed from the reaction mixture under reduced pressure, water
16. additionis added
17. filtrationThe formed precipitate is filtered off
18. customdried in vacuo